Lineage tracing aged mouse kidneys shows lower number of cells of renin lineage and reduced responsiveness to raas inhibition.

LINEAGE TRACING AGED MOUSE KIDNEYS SHOWS LOWER NUMBER OF CELLS OF RENIN LINEAGE AND REDUCED RESPONSIVENESS TO RAAS INHIBITION. Am J Physiol Renal Physiol. 2018 Feb 07;: Authors: Hamatani H, Eng DG, Kaverina NV, Gross KW, Freedman B, Pippin JW, Shankland SJ Abstract Blocking the renin-angiotensin-aldosterone system (RAAS) remains a mainstay of therapy in hypertension and glomerular diseases. With the population aging, our understanding of renin producing cells in kidneys with advanced age is more critical than ever. Accordingly, we administered tamoxifen to Ren1cCreERxRs-tdTomato-R mice to permanently fate map cells of renin lineage (CoRL). The number of Td-tomato labeled CoRL decreased significantly in aged mice (24m of age) compared to young mice (3.5m of age), as did renin mRNA levels. To determine if aged CoRL responded less to RAAS blockade, enalapril and losartan were administered over 25d following uninephrectomy in young and aged mice. The number of CoRL increased in young mice in response to enalapril and losartan. However, this was significantly lower in aged mice compared to young mice due to limited proliferation, but not recruitment. Gene expression analysis of laser captured CoRL showed a substantial increase in mRNA levels for pro-apoptotic and pro-senescence genes, and an increase in a major pro-senescence protein on immunostaining. These results show that CoRL are lower in aged mice, and do not respond to RAAS inhibit...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research